brca and nact in tnbc patients

Conditions: Triple-Negative Breast Cancer

Summary: the goal of this observational study is to evaluate data from patients with triple-negative breast cancer (tnbc) treated with neoadjuvant chemotherapy (nact) in order to better define the impact of germline brca1/2 (gbrca1/2) mutation status on outcomes in this patient population. the aims of the study are: * to evaluate the rate of pathologic complete response (pcr) in patients with locally advanced tnbc who performed nact, in relation to the mutational status of gbrca. * to evaluate evaluate event free survival (efs) and overall survival (os) in this patients population.

triple-negative breast cancer (tnbc) is characterized by earlier recurrence and shorter survival compared with other types of breast cancer. moreover, approximately 15 to 25% of all tnbc patients harbor germline brca (gbrca) 1/2 mutations, which confer a more aggressive phenotype. however, tnbc seems to be particularly sensitive to chemotherapy, the so-called 'triple negative paradox'. therefore, neoadjuvant chemotherapy (nact) is currently considered the preferred approach for early-stage tnbc. brca status has also been studied as a predictive biomarker of response to platinum compounds. although several randomized trials investigated the addition of carboplatin to standard nact in early-stage tnbc, the role of brca status remains unclear. in this retrospective analysis, data from 136 consecutive patients with stage i-iii tnbc who received standard nact, with or without the addition of carboplatin, will be evaluated in order to define clinical features and outcomes in brca 1/2 mutation carriers and non-carrier controls.

Eligibility criteria:
inclusion criteria: * written informed consent. * age older than 18 years. * unilateral or bilateral primary carcinoma of the breast, confirmed histologically by core biopsy. * tumor lesion in the breast with a palpable size of ≥ 2 cm and/or ≥ 1.5 cm by ultrasound or magnetic resonance imaging (mri). in case of inflammatory carcinoma, the extent of inflammation can be used as measurable lesion. * american joint commission on cancer stage ii or iii invasive breast cancer. * known estrogen (er)- and progesterone (pgr)-receptor negative tumors. * known her-2/neu negative tumors, defined as ihc 1+/2+ or sish not amplified. * patients suitable for neoadjuvant chemotherapy * eastern cooperative oncology group (ecog) performance status (ps) ≤2 or karnowsky performance status index at least 80%. * normal cardiac function must be confirmed by ecg and cardiac ultrasound (lvef or shortening fraction) within 1 month prior to registration. * laboratory requirements: * hematology: absolute neutrophil count (anc) ≥ 1.5 x 109/l, platelets ≥ 100 x 109/l, hemoglobin ≥ 10 g/dl. * hepatic function: total bilirubin \ 1.5 x unl associated with alkaline phosphatase \> 2.5 x unl are not eligible for the study. * renal function: creatinine ≤ 2 mg/dl, \< 1,25 unl (or the calculated creatinine clearance ≥ 60 ml/min). * paraffin tumor tissue block made available. * availability to provide the set up of the histological preparations for molecular analysis. * negative pregnancy test (urine or serum). * patients must be available and compliant for treatment and follow-up. exclusion criteria: * patients candidate for adjuvant chemotherapy. * evidence of distant metastasis. * prior chemotherapy for any malignancy. * prior radiation therapy for breast cancer. * pregnant or lactating patients. * inadequate general condition. * previous malignant disease. * known or suspected congestive heart failure (\>nyha i) and/or coronary heart disease, angina pectoris requiring antianginal medication, previous history of myocardial infarction, evidence of transmural infarction on ecg, un- or poorly controlled arterial hypertension, rhythm abnormalities requiring permanent treatment, clinically significant valvular heart disease. * history of significant neurological or psychiatric disorders that would prohibit the understanding and giving of informed consent.

Keywords: brca1/2 neoadjuvant chemotherapy platinum agents triple-negative breast ccancer